Bone morphogenetic protein-2 induces cyclin kinase inhibitor p21 and hypophosphorylation of retinoblastoma protein in estradiol-treated MCF-7 human breast cancer cells

Nandini Ghosh-Choudhury, Goutam Ghosh-Choudhury, Anthony Celeste, Paramita M Ghosh, Marissa Moyer, Sherry L. Abboud, Jeffrey Kreisberg

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

The biologic effects and mechanisms by which bone morphogenetic proteins (BMPs) function in breast cancer cells are not well defined. A member of this family of growth and differentiation factors, BMP-2, inhibited both basal and estradiol-induced growth of MCF-7 breast tumor cells in culture. Flow cytometric analysis showed that in the presence of BMP-2, 62% and 45% of estradiol-stimulated MCF-7 cells progressed to S-phase at 24 h and 48 h, respectively. Estradiol mediates growth of human breast cancer cells by stimulating cyclins and cyclin-dependent kinases (CDKs). BMP-2 significantly increased the level of the cyclin kinase inhibitor, p21, which in turn associated with and inactivated cyclin D1. BMP-2 inhibited estradiol-induced cyclin D1-associated kinase activity. Also estradiol-induced CDK2 activity was inhibited by BMP-2. This inhibition of CDK activity resulted in hypophosphorylation of retinoblastoma protein thus keeping it in its active form. These data provide the first evidence by which BMP-2 inhibits estradiol-induced proliferation of human breast cancer cells. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)186-196
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1497
Issue number2
DOIs
StatePublished - Jul 21 2000
Externally publishedYes

Keywords

  • BMP-2
  • Breast cancer cell
  • p21
  • pRb

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

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